Methods and compositions for inhibiting viral entry into cells

An isolated mammalian cell comprising an endogenous CD4, CXCR4 or CCR5 HIV receptor or co-receptor gene and an exogenous nucleic acid sequence encoding a fusion protein comprising a C34 peptide fusion inhibitor comprising the amino acid sequence as shown in SEQ ID NO:5 fused in frame to the N-terminal extracellular domain of a CXCR4 or a CCR5 protein, wherein a regulatory sequence is operatively linked to the nucleic acid sequence encoding the fusion protein, wherein the expression of the endogenous HIV receptor or co-receptor gene product in the cell is knocked out, and further wherein the fusion protein is membrane bound and the C34 peptide fusion inhibitor is expressed on the surface of the isolated cell.